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Identification of HAGHL as a novel metabolic oncogene regulating human colorectal cancer progression.
Xu, Yan; Zhou, Xiaojun; Gao, Ling; Yan, Su; Li, Zhenyun; Zhang, Daiyi; Pu, Jianhong; Zou, Shitao; Mao, Zhongqi.
Afiliação
  • Xu Y; Department of General Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, People's Republic of China.
  • Zhou X; Health Management Center, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, People's Republic of China.
  • Gao L; Department of General Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, People's Republic of China.
  • Yan S; Department of General Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, People's Republic of China.
  • Li Z; Health Management Center, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, People's Republic of China.
  • Zhang D; Health Management Center, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, People's Republic of China.
  • Pu J; Health Management Center, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, People's Republic of China.
  • Zou S; Health Management Center, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, People's Republic of China.
  • Mao Z; Suzhou Cancer Center Core Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, 16 Baita West Road, Suzhou, 215001, Jiangsu, People's Republic of China. stzoupku@126.com.
Clin Transl Oncol ; 25(4): 1033-1042, 2023 Apr.
Article em En | MEDLINE | ID: mdl-36417085
PURPOSE: Cancer development remains the most challenging obstacle in colorectal cancer (CRC) treatment. The current study aims to identify and demonstrate novel oncogenes for CRC. METHODS: The CRC data of the Cancer Genome Atlas database and the Gene Expression Omnibus database were subjected to bioinformatics analysis to identify the novel potential diagnostic and prognostic biomarkers for CRC. Immunohistochemical assay, western blot, and quantitative PCR (qPCR) were used to analyze hydroxyacylglutathione hydrolase-like (HAGHL) gene expression in CRC tissues and cultured CRC cells. D-Lactate colorimetric assay was applied to determine concentration of D-lactate in supernatants from CRC tissues and cell culture medium. Cell counting kit-8 (CCK-8) assay, flow cytometry, tumor xenografts experiment, and TUNEL staining analysis were performed to evaluate the function of HAGHL in CRC. RESULTS: We comprehensively analyzed the CRC data of the Cancer Genome Atlas database and the Gene Expression Omnibus database, and identified several novel potential diagnostic and prognostic biomarkers for CRC, including HAGHL, DNTTIP1, DHX34, and AP1S3. The expression of HAGHL, the strongest oncogenic activity gene, is positively related to D-lactate levels in CRC tissues and negatively associated with patient prognosis. HAGHL downregulation suppressed the production of D-lactate and induced apoptosis, resulting in inhibition of cell proliferation in vitro. In vivo experiment showed that knockdown of HAGHL induced cell apoptosis and inhibited tumor growth. CONCLUSION: These findings suggest that HAGHL acts as a novel metabolic oncogene and demonstrate the underlying mechanism by which HAGHL regulates CRC progression, highlighting its utility as a diagnostic and prognostic factor and as a potential therapeutic target for the treatment of CRC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / MicroRNAs Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Revista: Clin Transl Oncol Ano de publicação: 2023 Tipo de documento: Article País de publicação: Itália
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / MicroRNAs Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Revista: Clin Transl Oncol Ano de publicação: 2023 Tipo de documento: Article País de publicação: Itália